On December 22, 2022 Kite Pharma, Inc., a Gilead Company, (hereafter, Kite) (NASDAQ: GILD) and Daiichi Sankyo Co., Ltd. (hereafter, Daiichi Sankyo) (TSE: 4568) reported that the Japan Ministry of Health, Labour and Welfare (MHLW) has approved Yescarta (axicabtagene ciloleucel), a chimeric antigen receptor (CAR) T-cell therapy, for the initial treatment of patients with relapsed/refractory large B-cell lymphoma ( R/R LBCL): diffuse large B-cell lymphoma, primary mediastinal large B-cell lymphoma, transformed follicular lymphoma, and high-grade B-cell lymphoma (Press release, Kite Pharma, DEC 22, 2022, View Source [SID1234625564]). Yescarta should be used only in patients who have not received prior transfusion of CAR T-cells targeted at CD19 antigen.

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The Standard of Care (SOC) to treat LBCL patients has historically been a multi-step process that starts with chemoimmunotherapy, followed by high-dose chemotherapy (HDT) and then ends with a stem cell transplant (ASCT). Although approximately 60% of newly diagnosed LBCL patients will respond to the initial treatment with chemotherapy, 40% will relapse or will not respond and need second-line treatment. Yescarta is now approved for the initial treatment of R/R LBCL patients in Japan.

"We are very proud of this additional Yescarta approval in Japan," said Christi Shaw, CEO of Kite. "As Japan has the second-largest number of people diagnosed with non-Hodgkin lymphoma globally, this approval marks an important step in bringing this innovative therapy earlier to more patients."

"We are glad to have achieved this important milestone in order to provide an innovative treatment option to more patients with large B-cell lymphoma in Japan," said Wataru Takasaki, PhD, Executive Officer, Head of R&D Division in Japan, Daiichi Sankyo. "It also further demonstrates the expertise of our Daiichi Sankyo R&D organization as we had successfully expanded the indication for this CAR-T modality."

The approval of Yescarta for the initial treatment of R/R LBCL patients in Japan is based on clinical data, including the results of the global pivotal trial conducted by Kite (ZUMA-7). ZUMA-7 is the largest and longest trial of a CAR T-cell therapy versus SOC in this patient population. Results from the study demonstrated that at a median follow-up of two years, Yescarta-treated patients had a four-fold greater improvement in the primary endpoint of event-free survival (EFS; hazard ratio 0.40; 95% CI: 0.31-0.51, P<0.0001) over the current SOC (8.3 months vs 2.0 months). Additionally, Yescarta demonstrated a 2.5 fold increase in patients who were alive at two years without disease progression or need for additional cancer treatment vs SOC (41% v 16%).

This indication was first approved by the U.S. FDA in April 2022 followed by the European Commission in October 2022.

On December 7, 2022, Daiichi Sankyo and Kite jointly announced that the Marketing Authorization for Yescarta will be transferred to Gilead Sciences K.K., the Japan subsidiary of Gilead Sciences, Inc., in 2023. The Kite Cell Therapy Business Unit at Gilead Sciences K.K. will manage the sales and promotion activities of the product in Japan after the Marketing Authorization transfer.

Kite’s manufacturing facility in El Segundo, California, U.S., has been approved by Japanese regulatory authorities to commence manufacturing Yescarta for the Japan market in 2023.

About Zuma-7

ZUMA-7 is an ongoing, randomized, open-label, global, multicenter (US, Australia, Canada, Europe, Israel) Phase 3 study of 359 patients at 77 centers, evaluating the safety and efficacy of a single-infusion of Yescarta versus current SOC for second-line therapy (platinum-based salvage combination chemotherapy regimen followed by high-dose chemotherapy and autologous stem cell transplant in those who respond to salvage chemotherapy) in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The primary endpoint is event free survival (EFS). Key secondary endpoints include objective response rate (ORR) and overall survival (OS). Additional secondary endpoints include patient reported outcomes and safety.

About YESCARTA

Yescarta (axicabtagene ciloleucel) is a CAR T-cell therapy directed against CD19 (a cell membrane protein), which harnesses a patient’s own immune system to fight cancer. Axicabtagene ciloleucel is made by removing a patient’s T cells from their blood and engineering them in the lab to express chimeric antigen receptors so that they can recognize and destroy cancer cells when they are infused back to the patient’s body. The CAR T-cell therapy is manufactured specifically for each patient and administered only once. Axicabtagene ciloleucel received Orphan Drug Designation from the Japan MHLW in 2018 for the treatment of diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, transformed follicular lymphoma and high-grade B-cell lymphoma. Yescarta was approved in Japan for the treatment of patients with relapsed or refractory large B-cell lymphomas, a type of non-Hodgkin lymphoma, in January 2021.

Please see full U.S. Prescribing Information, including BOXED WARNING and Medication Guide.

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of:

Adult patients with large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy. (1.1)
Adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma.
Limitations of Use: Yescarta is not indicated for the treatment of patients with primary central nervous system lymphoma. (1.1)

Adult patients with relapsed or refractory follicular lymphoma (FL) after two or more lines of systemic therapy. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). (1.2)
For the full European Prescribing Information, please visit: : View Source

On December 22, 2022 Elpiscience Biopharmaceuticals, Inc. ("Elpiscience"), a clinical-stage biopharmaceutical company focused on developing next-generation immunotherapies to benefit cancer patients worldwide, reported that the Center of Drug Evaluation (CDE) has cleared Elpiscience’s Investigational New Drug Application (IND) for ES014 to initiate a Phase 1 clinical study for patients with advanced solid tumors (Press release, Elpiscience, DEC 22, 2022, View Source [SID1234625563]). ES014 is a first-in-class anti-CD39xTGF-β bispecific antibody (bsAb) that simultaneously targets the CD39-adenosine and TGF-β pathways to synergistically activates T cells for ICB-resistant cancer immunotherapy.

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"We are delighted that our IND for ES014 was cleared by CDE. Solid tumors frequently express TGF-β, which suppresses T cell activation and induces CD39 expression, the rate-limiting enzyme in the ATP-adenosine pathway. The anti-CD39 target is designed to selectively direct ES014 to the TME where CD39 expression level is high and the anti-TGF-β activity promotes effector T cell entry into TME, resulting in immune activation and eventually tumor killing, while avoiding or minimizing systemic immunotoxicity," said Dr. Hongtao Lu, Co-Founder and Chief Scientific Officer of Elpiscience.

ES014’s anti-CD39 activity aims to reverse TME immunosuppression by reducing suppressive adenosine, while maintaining high levels of immune-stimulatory extracellular ATP. The combined removal of immune suppression and immune stimulating effects of ES014 were recently demonstrated in a PD-1 antibody non-responsive in vivo animal model where tumor growth was significantly inhibited after treatment.

"ES014 is an innovative product targeting suppressive tumor microenvironment, aiming to convert ‘cold’ tumor into ‘hot’ tumor by simultaneously blocking ATP-adenosine and TGF-beta pathways, the two most important suppressive pathways within TME. In ex vivo human cancer 3D studies, ES014 has demonstrated excellent ability in promoting CD8 T cell survival and T cell cytotoxicity towards cancer. We look forward to seeing cancer patients deriving benefit in our Phase 1 study," said Dr. Steve Chin, Chief Medical Officer of Elpiscience.

On December 22, 2022 OSE Immunotherapeutics SA (ISIN: FR0012127173; Mnemo: OSE) reported that the first patient has been dosed in the Phase 1/2 clinical trial evaluating OSE-279, a high affinity anti-PD1 blocking monoclonal antibody, in patients with advanced solid tumors or lymphomas (Press release, OSE Immunotherapeutics, DEC 22, 2022, View Source [SID1234625562]).

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This first-in-human open label Phase 1/2 dose escalation and expansion study aims to determine the Maximum Tolerated Dose and/or the recommended Phase 2 dose of OSE-279 as a monotherapy in advanced solid tumors or lymphomas. Secondary objectives include assessment of OSE-279’s antitumor activity, evaluation of the safety profile, pharmacokinetic and receptor occupancy or pharmacodynamic profile.

OSE-279 is a high affinity humanized anti-PD1 monoclonal antibody blocking both PD-L1 and PD-L2, the ligands of PD1 overexpressed by tumor cells and tumor microenvironment. Overexpression of PD-L1 and PD-L2 on tumor cells and other cell types of the tumor microenvironment is a mechanism of tumor immune escape.

OSE-279 is the key anti-PD-1 backbone component of OSE’s bifunctional checkpoint inhibitor BiCKI platform that is targeting PD1 and other new immune targets. The first cytokine selected to be paired with the anti-PD1 in the bispecific antibody is Interleukin-7 (IL-7), which has been shown at preclinical stage to improve long-term immune functions and cancer immunotherapy efficacy. BiCKI-IL-7 has potential to address the needs of a patient population in immune escape from checkpoint inhibitor treatment.

Nicolas Poirier, Chief Executive Officer of OSE Immunotherapeutics, comments: "We are very excited to begin first-in-human testing with our proprietary high affinity anti-PD1 monoclonal antibody, which is covered by a strong global patent portfolio in the US, Europe, Asia and South America. Dosing of the first patient marks a significant milestone in the development of OSE-279, and we look forward to the first results assessing the therapeutic potential of OSE-279 as a monotherapy treatment. Further internal clinical development of OSE-279 as a monotherapy would be conducted in pre-identified cancer niche indications to address patients with high unmet medical needs despite immuno-sensitive tumor type. This first clinical study will also allow us, at a later stage, to explore OSE-279, the backbone of OSE’s BiCKI platform, in combination with other OSE drug candidates or with external assets accessed through potential new partnerships with biotech or pharmaceutical companies."

Given the advantages of owning a proprietary and protected anti-PD1 antagonist antibody in the new era of immuno-oncology, OSE Immunotherapeutics has developed a global intellectual property strategy protecting OSE-279 until at least 2039. This has been achieved through the grant in 2022 of patents for the US, Europe, China, Japan, Korea, Australia and Mexico to date. These patents protect the antibody sequences of OSE-279 associated with its innovative biological and manufacturing properties.

On December 22, 2022 SamanTree Medical, a medical technology company driven to support clinicians with their intraoperative decisions and improve cancer surgery outcomes, reported the publication of clinical data in prostate cancer, expanding the potential clinical utility of its proprietary medical imaging platform, the Histolog Scanner (Press release, SamanTree Medical, DEC 22, 2022, View Source [SID1234625561]).

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Morphological information is the gold standard guidance for clinicians in cancer surgery allowing the visualization of microscopic cancer lesions, however, the time required to get the results is a limiting factor to its widespread and routine use (Dobbs et al., 2013; Elfgen et al., 2019). Accurate intraoperative assessment is especially important in prostate cancer, where nerve-sparing surgery can avoid impotency and urinary incontinency that may affect many of the patients (Dinneen et al., 2019). Such surgery implies however leaving nerves surrounding the prostate intact while removing as much cancer as possible, representing a potential site for recurrences if cancer has invaded them.

The Enclosure Study was conducted at Canisius Wilhelmina Hospital (Netherlands), under the supervision of Professor Diederik Somford and Dr. Willem Vreuls. The study evaluated the Histolog Scanner as an alternative to NeuroSAFE. "Surgeons are most of the time guided with preoperative MRI, which does not enable cellular visualization of the nerve-adjacent areas of the prostate, resulting in 20-40% positive margins found by final pathology examination following surgery. The current best practice to avoid the risk of positive margins is to perform frozen sections of the nerve-adjacent structures of the prostate, a procedure called NeuroSAFE. This procedure requires time and resources, limiting its standardization amongst hospitals. Enclosure study shows the relevance of the information provided by the Histolog Scanner resulting in similar performance to NeuroSAFE procedure, however with 80% time reduction", explained Dr. Willem Vreuls.

Charles S. Carignan, MD, SamanTree Medical Chairman commented, "as already announced in our previous press release, the Histolog Scanner is a multi-purpose imaging platform compatible with multiple clinical routine, for faster and safer oncological treatment. With its large field of view and high resolution, the Histolog Scanner provides a unique opportunity to standardize intraoperative assessment in indications where morphologic information cannot be obtained in a time-efficient, cost-effective manner, such as prostate. The numbers speak for themselves; the Histolog Scanner was shown to provide the gold standard information in 5 minutes instead of 45. In cases where frozen sections are performed as intraoperative assessment, the Histolog Scanner provides surgeons and pathologists with a faster communication channel while keeping the microscopic resolution. Another demonstration of that will be published early 2023 with the utilization of our platform in brain cancer."

A few words on brain cancer:

Earlier this month at the congress Digital Pathology & AI, the medical team from Leeds Teaching Hospital Trust (UK), presented promising results showing that the Histolog Scanner enabled the assessment of brain tissue with 100% agreement with frozen section analysis, but again with drastic time reduction. Additional details from this study will be published soon.

On December 22, 2022 Merck, a leading science and technology company, reported a research collaboration and commercial license agreement with Mersana Therapeutics, Inc., Cambridge, Massachusetts, USA to discover novel antibody-drug conjugates (ADCs) leveraging Mersana’s proprietary Immunosynthen STING-agonist ADC platform, directed against up to two targets (Press release, Merck & Co, DEC 22, 2022, View Source [SID1234625560]). The Immunosynthen platform is designed to generate systemically administered ADCs that locally activate STING signaling in both tumor-resident immune cells and in antigen-expressing tumor cells, unlocking the anti-tumor potential of innate immune stimulation.

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"Building on our deep expertise and portfolio of two clinical and nine preclinical assets in the ADC space, we are focused on the discovery of next-generation state-of-the-art ADC drugs," said Paul Lyne, Head of Research Unit Oncology at the Healthcare business sector of Merck. "An approach that can directly target the tumor microenvironment with an immunomodulatory ADC has the potential to bring the benefits of this immunotherapy to a broader group of patients. This collaboration with Mersana to design novel immunostimulatory ADCs that can harness the potential of the STING pathway is an ideal complement to our innovation in this area."

The STING pathway is a fundamental means of generating innate immune response that can lead to anti-tumor activity and immunological memory. Mersana has generated preclinical data demonstrating Immunosynthen’s ability to enable highly targeted STING activation within both tumor cells and tumor resident myeloid cells while avoiding unwanted systemic effects.

"We are pleased to be partnering with Merck in a collaboration designed to extend the reach of our Immunosynthen platform and bring novel new product candidates forward with the potential to benefit patients," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics.

Under the terms of the agreement, Mersana will develop novel ADC product candidates against up to two targets utilizing its Immunosynthen platform to conjugate proprietary antibodies from Merck.

Mersana will receive an upfront payment of $30 million. Mersana is also eligible to receive reimbursement of certain costs, up to $800 million in potential regulatory, development and commercial milestone payments, and up to low double-digit percentage royalties on worldwide net sales of any approved ADCs developed under the agreement.

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